The ERG (ETS-related gene) proto-oncogene is overexpressed in a majority of prostate tumors as a result of a gene fusion involving TMPRSS2 and ERG. Petrovics et al. 2005 Oncogene 24: 3847-3852; Tomlins et al. 2005 Science 310: 644-647; Kumar-Sinha et al. 2008 Nat. Rev. Cancer 8: 497-511. The TMPRSS2/ERG fusion results in the overexpression of N-terminally truncated or full-length forms of ERG. Klezovitch et al. 2008 Proc. Natl. Acad. Sci. USA 105: 2105-2110; and Sun et al. 2008 Oncogene 27: 5348-5353. Various studies have underscored the causative oncogenic function of ERG in prostate cancer. Klezovitch et al. 2008 Proc. Natl. Acad. Sci. USA 105: 2105-2110; Tomlins et al. 2008 Neoplasia 10: 177-188; Sun et al. 2008 Oncogene 27: 5348-5353; Wang et al. 2008 Cancer Res. 68: 8516-24.
Poor disease outcome for subjects with tumors harboring duplications of TMPRSS2/ERG fusions or chromosomal losses (Edel) associated with the fusion event has been highlighted. Attard et al. 2008 Oncogene 27: 253-263; FitzGerald et al. 2008 BMC Cancer 8: 230; Mehra et al. 2008 Cancer Res 68: 3584-3590.
An unmet medical need thus exists for new treatments for TMPRSS2:ERG positive prostate cancer.